Risk of Cardiomyopathy in Younger Persons With a Family History of Death from Cardiomyopathy: A Nationwide Family Study in a Cohort of 3.9 Million Persons
Background—Recommendations for pre-symptomatic screening of relatives of cardiomyopathy patients are based on findings from tertiary centers. Cardiomyopathy inheritance patterns are fairly well understood, but how cardiomyopathy in younger persons (<50 years) aggregates in families at the population level is unclear. In a nationwide cohort, we examined the risk of cardiomyopathy by family history of premature death (<60 years) from cardiomyopathy.
Methods and Results—By linking Danish national register data, we constructed a cohort of 3.9 million persons born from 1950 to 2008. We ascertained family history of premature (<60yrs) death from cardiomyopathy or other conditions, and cohort members were followed from 1977 to 2008 for cardiomyopathy diagnosed at <50 years. We identified 3,890 cardiomyopathies in 89 million person-years of follow-up. Using Poisson regression, we estimated incidence rate ratios for cardiomyopathy by family history of premature death. Premature cardiomyopathy deaths in first- and second-degree relatives were associated with 29- and 6-fold increases in the rate of cardiomyopathy, respectively. If the first-degree relative died aged <35yrs, the rate of cardiomyopathy increased 100-fold; given ≥2 premature deaths in first-degree relatives, the rate increased more than 400-fold. In contrast, a family history of premature death from other cardiac or non-cardiac conditions increased the rate of cardiomyopathy 3-fold at most.
Conclusions—A family history of premature cardiomyopathy death was associated with an increase in risk of cardiomyopathy ranging from 6- to 400-fold, depending on age, kinship, gender and number of affected family members. Our general population-based results support recommendations for pre-symptomatic screening of relatives of cardiomyopathy patients.
- premature death
- familial hypertrophic cardiomyopathy
- family history
- risk factor
- cohort study
- Received September 25, 2014.
- Revision received May 25, 2015.
- Accepted July 6, 2015.